acids bases buffers and disorders by dr. ashok kumar j

- it donates proton B– is an anion liberated by the deprotonation of

the acid, so it is called conjugate

base8/19/2014 2

Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry

8/19/2014 3Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry

Example Acid-Base Reactions


e.g. HCl ——> H+(aq) + Cl¯(aq)

HNO3——> H

+(aq) + NO

3¯(aq)

H2SO

4——> 2H

+(aq) + SO

4

2-(aq)


2. Weak acids get dissociated partiallyConjugate bases of these acids are strong (have greater affinity for proton).e.g.: acetic acid

CH3COO-(aq) + H+(aq)

Carbonic acid is a weak acid – formed by hydration of carbon dioxide


Equilibrium constant for ionization reaction iscalled ionization or dissociation constants (Ka)


[B–]pH pKa log10

[BH]


value of pKa is lower for strong acids and higher for weak acids


Mechanism of Buffer Action

Acetate bufferCH3COO H / CH3COONa


Estimated by calculating the amount of

or required to change the pH of one

liter of buffer by one unit.



[Base]pH pKa log10

[Acid]

8/19/2014 Dr. ASHOK KUMAR .J.; Professor; Dept. Biochemistry 19

Significance of pH

1. Isoelectric pH

2. Optimum pH

3. Tautomeric forms of purine and pyrimidineNH2 ---- = NHC-OH ----- C=O

Normal pH of

blood

7.35 7.45

Average 7.4


Bicarbonate BufferPhosphate BufferProtein BufferHemoglobin bufferAmmonia buffer



• Normal pCO2 of arterial blood is 40 mmof Hg• Normal carbonic acid concentration is 1.2 mmol/L• pKa of carbonic acid is 6.1

[Bicarbonate]pH pKa log10

[Carbonic acid]

[24]pH log10

[1.2]

pH log10 20

pH

pH


• NaH2PO4 – is excreted in urine daily- Normal excretion is 30mEq/L


CO2

Cl- Cl-

PlasmaErythrocyte


Kidney plays a major role in acid-base regulation

2. Reclaimation the bicarbonate ions present in the ultrafiltrate

1. Excretion of H+

3. Excretion of titrable acid and ammonia

4. Excretion of ammonia


HCO3-HCO3

-

H2O + CO2 H2CO3-

H+ H+

Tubular cell Tubular Lumen

Na+Na+


HCO3-HCO3

-

H2O + CO2 H2CO3-

H+ H+ HCO3-+

H2CO3-

H2OCO2 +CO2



When there is an excess of acid production in the body, H+ are excreted in urine as titrableacid and ammonia


HCO3-

H2O + CO2 H2CO3-

H+

NH4+

H+


NH3

Titrable acid

Na2HPO4-

NaH2PO4-

GLUTAMIN

GLUTAMATE

Glutaminase NH3


Anion Gap

In Extracellular fluidSum of anions = Sum of cations

- Electrical neutrality

•Sodium (Na+) and Potassium (K+) together accounts for 95% of the cations

•Chloride and bicarbonate accounts for only 86% of the anions

•Theses are the electrolytes commonly measured

• Measured cations

Sodium 136 mEq/L

Potassium 4 mEq/L

• Unmeasured Cation

Calcium 4.5 mEq/L

Magnesium 1.5 mEq/L

• Measured anionsChloride 98mEq/LBicarbonate 25mEq/L

• Unmeasured anionProtein 15mEq/LPhosphate 2mEq/LOrganic acids 5mEq/LSulfate 1mEq/L



Unmeasured anions constitute the anion gap

Calculated as difference between measured cations and measured anions

Anion Gap = (Na+ + K+) - (Cl- + HCO3-)

= ( 140 + 4) – (103 + 25)= 16

Normal is about 12 mEq/L


Acidosis : Clinical state where acids accumulate or bases are lost

Alkaosis : Clinical state where accumulation of base or loss of acids


[Carbonic acid]


[Bicarbonate][Carbonic acid]

pH pKa log10

Regulated by KidneyMetabolic component

Decreased BicarbonateDecreases the ratioDecreases pH

Increased Carbonic acidDecreases the ratioDecreases pH

Regulated by lungsRespiratory component


[Bicarbonate][Carbonic acid]

pH pKa log10

Regulated by KidneyMetabolic component

Increased BicarbonateIncreases the ratioIncreases pH

Decreased Carbonic acidIncreases the ratioIncreases pH

Regulated by lungsRespiratory component


1. Metabolic acidosis :- Primary alkali deficit

2. Metabolic acidosis :- Primary alkali excess

3. Respiratory acidosis :- Primary carbonic acid excess

4. Respiratory alkalosis :- Primary carbonic acid deficit

pH pKa log10[Bicarbonate][Carbonic acid]



[Carbonic acid]

• Acid base disturbances will be followed by compensatory change in counteracting variable

e.g

a. Primary change in bicarbonate involves alteration in pCO2

b. Primary increase in arterial pCO2 involves an increase in arterial bicarbonate

• Compensatory changes try to restore the pH normal

• Compensatory changes cannot fully correct a disturbance



1. UncompensatedCompensatory mechanism has not begun

2. Partially compensatedCompensatory mechanism has begun pH is not yet normal

3. Fully compensatedCompensatory mechanism has brought pH to normal


Increased production of hydrogen ions

Impaired excretion of hydrogen ions

Loss of bicarbonate from the gastrointestinal tract or in urine

Ingestion of hydrogen ions or drugs which are metabolized to acids


Production of organic acids exceeds the rate of elimination

Acidosis may be accompanied by loss of cations, that are excreted with anions

Acids are nutralized by alkali – bicarbonate concentration decreases

“Primary alkali deficit”


Causes :1. Increased production of organic acids

like acetoacetic acid , 3-OH butyric acid & lactic acid

Diabetic ketoacidosis, Starvation ketoacidosis,Lactic acidosis


2. Salicylate intoxicationGenerally occurs with blood salicylate level above 30 mg/dl

Salicylate stimulates respiratory centre

3. Paraldehyde toxicityPathogenesis is ill defined ; Acidosis

may actually due to ketosis ; due to 3 OH butyric acid as the main acid product


4. Isoniazide – is antimicobacterial agent- may be hepatotoxic- significant liver damage- impairs clearance of lactate

5. Iron toxicity – production of toxic peroxides- Mitochondrial poison- Interferes with normal cellular

respiration- Lactate is formed


6. Tissue hypoxia – Anaerobic metabolism- Accumulation of organic

acids

In all these conditions there is increased anion gap


7. Loss of Na+, K+, & bicarbonate from gastrointestinal tract ( as in diarrhoea)

Loss of bicarbonate is replaced by chlorideResults in hyperchloremic acidosis

8. Ureterosigmoidostomy- Metabolic acidosis


8. Acidosis can be due to administration of ammonium chloride, lysine, argininehydrochloride – due to formation of HCl

9. Aldosteron stimulates distal tubular acid and potassium secretion

In hyporaldosteronism loss of this effect leads to metabolic acidosis


10. Renal tubular acidosisLoss of bicarbonate due to decreased tubular secretion of H+

Type I or Distal renal tubular acidosisAbsorption of bicarbonate is

defectivepH of urine is >5.5Compensatory increase in

chloride (Hyperchloremic acidosis)

• Type II or proximal renal tubular acidosis

Secretion of hydrogen ions is defective

pH of urine is < 5.5

Potassium is normal

Type IV due to resistance to aldosterone

pH <5.5

Hyperkalemia


BUFFER SYSTEM

Mainly HCO3/ carbonic acid minimizes change in pH

HCO3 concentration is decreased and ratio of HCO3/H2 CO3 less

than 20/1

RESPIRATORY MECHANISM

Increases rate and depth of respiration (Kussumauls breathing)

Elimination of carbonic acid as CO2 ,

Decrease in pCO2 and consequently decrease in H2 CO3


RENAL MECHANISM

Increases excretion of acid and preserves the base

by increased rate of Na- H exchange

Increases ammonia formation and increased

reabsorption of HCO3


Uncompensated Metabolic acidosisPartiallycompensated Metabolic acidosisCompensated Metabolic acidosis

Fully compensated

Partially compensated

uncompensated

NormaldecreaseddecreasedpH

DecreaseddecreasednormalpCO2

DecreaseddecreaseddecreasedHCO3

pO2


Metabolic alkalosis

• Therapeutic administration of large dose of alkali – chronic intake of excess antacids

- Intravenous administration of bicarbonate


RESPIRATORY MECHANISM:

Increase in pH depresses the respiratory center,

causes retention of CO 2 which in turn increases the

H 2CO 3 .

RENAL MECHANISM:

Kidney decreases Na –H+ exchange,

decreases the formation of ammonia

decreases reclamation of bicarbonate.

Fully compensated


uncompensated

normalincreasedincreasedpH

increasedincreasednormalpCO2

increasedincreasedincreasedHCO3

pO2



Weakness of respiratory muscles


BUFFER SYSTEM

Excess carbonic acid is buffered with haemoglobin and

protein buffer

RESPIRATORY MECHANISM

Increase in pCO2 stimulates respiratory center

Increase in rate and depth of respiration provided the

defect is not in respiratory center.


RENAL COMPENSATION

Na-H+ exchange

Ammonia formation

Reclamation of HCO3

Fully compensated


uncompensated

normaldecreaseddecreasedpH

increasedincreasedincreasedpCO2

increasedincreasednormalHCO3

pO2


Fully compensated


uncompensated

NormalIncreased IncreasedpH

DecreasedDecreasedDecreasedpCO2

DecreaseddecreasedNormalHCO3

pO2



BUFFER SYSTEM

RBC and tissue buffers provide H+ that

consumes HCO3

RENAL COMPENSATION

Decreased reclamation of HCO3

Thank you


acids bases buffers and disorders by dr. ashok kumar j

Health & Medicine